Quantitative determination of dopamine receptor subtypes not linked to activation of adenylate cyclase in rat striatum.

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Abstract
The binding of [3H]domperidone and [3H]spiroperidol was examined in membranes prepared from rat striatum. Scatchard analysis of the binding of [3H]domperidone resulted in curvilinear plots consistent with the presence of multiple classes of binding sites. Nonlinear regression analysis of untransformed data showed that the curvature was best explained by the presence of 2 populations of binding sites. Scatchard plots of the binding of [3H]spiroperidol were linear, suggesting that this radioligand binds to a single class of receptors. Results obtained in studies of the inhibition of [3H]spiroperidol binding by a number of competing ligands were not consistent with the interaction of these agents with a single class of binding sites. Computer-assisted analysis of the Hofstee plots of 6 competing ligands gave the same relative proportion for 2 classes of sites as determined by analysis of the binding of [3H]domperidone. The 2 classes of receptors labeled with [3H]spiroperidol had affinities for domperidone that were similar to those of the 2 populations of binding sites for [3H]domperidone. The number of binding sites for [3H]spiroperidol was equal to the total number of binding sites for [3H]domperidone. Evidently, the 2 radioligands bind to the same 2 classes of binding sites. It is unlikely that either of the 2 classes of striatal sites are receptor for serotonin. This approach will make it possible to assess the effects of physiological or pharmacological manipulations on the densities or properties of subtypes of dopamine receptors.